rs10483810

Positions:

• chr14-68526257-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321821.2(RAD51B):​c.1036+58007G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0672 in 152,222 control chromosomes in the GnomAD database, including 451 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.067 (451 hom., cov: 33)
• Consequence: RAD51B NM_001321821.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

Genes affected

RAD51B (HGNC:9822): (RAD51 paralog B) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are evolutionarily conserved proteins essential for DNA repair by homologous recombination. This protein has been shown to form a stable heterodimer with the family member RAD51C, which further interacts with the other family members, such as RAD51, XRCC2, and XRCC3. Overexpression of this gene was found to cause cell cycle G1 delay and cell apoptosis, which suggested a role of this protein in sensing DNA damage. Rearrangements between this locus and high mobility group AT-hook 2 (HMGA2, GeneID 8091) have been observed in uterine leiomyomata. [provided by RefSeq, Mar 2016]

LOC124903334 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1036+58007G>T		intron_variant			NP_001308750.1
RAD51B	NM_133509.5	c.1036+58007G>T		intron_variant			NP_598193.2
RAD51B	NM_001321812.1	c.1037-13943G>T		intron_variant			NP_001308741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1036+58007G>T		intron_variant		1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1036+58007G>T		intron_variant		1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1036+58007G>T		intron_variant		1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.0673 AC: 10232 AN: 152104 Hom.: 451 Cov.: 33

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.00712

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.0796

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0672 AC: 10229 AN: 152222 Hom.: 451 Cov.: 33 AF XY: 0.0676 AC XY: 5030 AN XY: 74424

Gnomad4 AFR AF: 0.0155

Gnomad4 AMR AF: 0.0559

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.00694

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0922

Gnomad4 OTH AF: 0.0787

Alfa AF: 0.0788 Hom.: 82

Bravo AF: 0.0609

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10483810; hg19: chr14-68992974;